P1390: NEW AND UPDATED RESULTS FROM A MULTICENTER OPEN-LABEL GLOBAL PHASE3 STUDY OF TAB-CEL FOR EBV+PTLD FOLLOWING HCT OR SOT AFTER FAILURE OF RITUXIMAB OR RITUXIMAB+CHEMOTHERAPY (ALLELE)
Authors: Mahadeo Kris Michael, Baiocchi Robert, Beitinjaneh Amer, Chaganti Sridhar, Sylvain Choquet, Daan Dierickx, Dinavahi Rajani, Laurence Gamelin, Armin Ghobadi, Guzman-Becerra Norma, Joshi Manher, Mehta Aditi, Nikiforow Sarah, Reshef Ran, Ye Wei, Prockop Susan
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Tab-cel is an off-the-shelf, allogeneic EBV-specific T-cell immunotherapy being studied in relapsed/refractory (r/r) EBV+ PTLD, an ultra-rare disease with poor overall survival (OS) and no approved PTLD therapies. Tab-cel has demonstrated an objective response rate (ORR) of >50% and >80% 2 yr OS in responders (Prockop JCI 2020) and safety data in >180 patients (pts) show tumor flare reaction (TFR) as the only identified risk. We previously presented data from the first P3, multicenter, open-label, global study of tab-cel-for EBV+ PTLD post HCT or SOT where R±CT failed (ALLELE; NCT03394365). Aims: Report updated outcomes (more pts, longer follow up) from ALLELE. Methods: Pts receive tab-cel at 2x106 cells/kg on days 1, 8, and 15 in 35-day cycles. Primary endpoint is ORR (evaluated per IORA using Lugano with LYRIC modification). Results: As of Nov 2021, 43 pts (14 HCT, 29 SOT) received ≥1 tab-cel dose (median 2 cycles [range 1–6]). 67.4% of pts had diffuse large B-cell lymphoma; 76.7% had extranodal disease at screening. Among pts aged ≥16 yrs, 27.5% had an ECOG score ≥2, and 42.5%/47.5% were high/intermediate risk per PTLD-adapted prognostic index. Median number of prior systemic treatment was 1 (range, 1–5). Overall ORR was 51.2% (22/43, 95% CI: 35.5, 66.7), 50.0% (7/14, 95% CI: 23.0, 77.0) in HCT, and 51.7% (15/29, 95% CI: 32.5, 70.6) in SOT, with a best overall response of CR (n=6, HCT; n=6, SOT) or PR (n=1, HCT; n=9, SOT; Table). Median TTR was 1.0 mo (0.7–4.7). 12/22 responders had DOR >6 mo, and median DOR was 23.0 mo (95% CI: 6.8, NE) [Table]. Overall median OS was 18.4 mo (95% CI: 6.9, NE), not yet reached in HCT (95% CI: 5.7, NE), and 16.4 mo in SOT (95% CI: 5.0, NE). Overall 1-yr OS rates were 61.1% (95% CI: 43.7, 74.5) [Figure], 70.1% in HCT (95% CI: 38.5, 87.6), and 56.2% in SOT (95% CI: 34.6, 73.2) [Table]. Pts responding to tab-cel had higher 1 yr OS rate (84.4%) vs non-responders (34.8%) [Table]. A univariate analysis generally showed similar efficacy across baseline characteristics; data on ECOG (<2 vs ≥2), extranodal disease and number of prior therapies (1 vs >1) will be shown. Serious treatment-emergent AEs (TEAEs) and fatal TEAEs were reported in 57.1% and 7.1% of HCT and 51.7% and 13.8% of SOT pts respectively. The safety profile was favorable and consistent with previous data, with no reports of TFR, infusion reactions, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, marrow rejection, or transmission of infectious diseases. No fatal TEAEs, GvHD or organ rejection were reported as tab-cel related. Summary/Conclusion: Updated ALLELE P3 data, which included additional pts and longer follow-up, confirm that tab-cel provides consistent clinically meaningful outcomes, including improved overall ORR, prolonged DOR and OS, and no safety concerns seen with other adoptive T-cell therapies, making it a potentially transformative treatment advance for r/r EBV+ PTLD.Keywords: EBV, Post-transplant lymphoproliferative disorder